The glycoprotein molecules of influenza type A virus will be studied at the level of their individual antigenic determinants (viz. epitopes) by means of monoclonal hybridoma antibodies. The antigenicity of the glycoprotein molecules of A/PR/8/34 (HON1) will be characterized with regard to the topographic relationship that exists among individual epitopes, the relation of selected epitopes to the polypeptide structure and their relevance in functional anti-viral assays in vitro and in vivo. The mechanism of antigenic drift will be analyzed by comparing the frequency of antigenic changes occurring in individual glycoprotein epitopes of various influenza type A isolates and of other members of the myxovirus family during replication in different host systems. The repertoire of distinct antigenic drift available to the glycoproteins will be assessed by antigenic analysis of a large panel of first generation variants of PR8 selected with many different hybridoma antibodies. The epidemiological relevance of increasing antigenic drift (exhibited by viral glycoprotein mutants selected sequentially in vitro with monoclonal antibodies) will be assessed by analysis of the overall antigenicity of the glycoproteins with ferret sera and by investigation of its effect on the virus-"immune"-host interaction in an animal model system.